ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.757G>T (p.Val253Phe) (rs748964205)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519193 SCV000618045 likely pathogenic not provided 2017-03-22 criteria provided, single submitter clinical testing The V253F variant in the GCK gene has been reported previously in patients with GCK-related MODY (Constantini et al., 2015; Rajab et al., 2015). The V253F variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). It is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants at the same codon (V253L/A) and in nearby residues (E248K, G249S/A, R250C/P, M251V/K/T/I, C252G/R/Y/S, N254H, T255A/I/S, E256K/D, W257R, G258S/R/C/D) have been reported in the Human Gene Mutation Database in association with MODY (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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